Tag Archives: hormones

This study found that hormone therapy reduced symptoms of psychological distress, although surgery had no further effect.

However, this conclusion is undercut by the fact that one person committed suicide during follow-up,* treatment did not reduce the prevalence of suicide attempts, and 17% of the people surveyed after treatment reported suicidal thoughts.

There are also areas where the methodology of the study could be improved.

Finally, the data on the percentages of suicide attempts is confusing. See the end of this review for details on the data.

Over 90% of patients said that they were happier and felt better about their body after treatment, but 17% reported that they had suicidal thoughts.

The improvement in psychological symptoms happens after hormone therapy. Surgery did not cause a significant change in psychopathology, although patients reported slightly more symptoms after surgery than after hormone therapy.

When asked, 57.9% of patients said that they experienced the most improvement after hormone therapy, 31.6% experienced the most improvement after surgery, and 10.5% experienced improvement just from being diagnosed.

After treatment, the average scores of psychopathology were similar to the general population.

After hormone therapy, none of the average subscale scores were different from the general population. However, after surgery, the group’s average scores for sleeping problems (p=0.033) and psychoticism (p=0.051) were higher than the general population.

These results raise some important questions.

What can we do to reduce suicide, suicide attempts, and suicidal thoughts in transgender people who have transitioned?

Why didn’t the percentage of suicide attempts go down when people were reporting fewer symptoms of depression?

Why didn’t surgery improve the mental well-being of the patients?

There were also a couple of important methodological questions that the authors did not discuss.

Combining the results of different treatments

As often happens, the study lumped together trans men (born female) and trans women (born male). The treatments for trans women and trans men involve different medications and surgeries. It is possible that androgens and estrogens have different effects on mood. Similarly, it might be that some surgeries are more beneficial to mental health than others or that some surgeries are more stressful than others.

The participants in the study were 46 trans women and 11 trans men. The authors do not discuss whether they differed in their mental health symptoms or social well-being. Nor do they give information on the gender of the people who completed the questionnaires at follow-up.

The study does not specify exactly what medications and dosages were used for the hormone therapy. They do not say exactly what surgeries the patients got.

Missing Data

As with many longitudinal studies, they did not have follow-up data on all of the participants due to incomplete questionnaires. In addition, one participant did not complete a questionnaire at the beginning of the study.

Thus, 56 people completed a questionnaire about their mental health before treatment, but only 47 people completed the questionnaire after hormone treatment. The authors then compared the average scores on the baseline questionnaires to the averages on the questionnaires after hormones.

It is possible that this would lead to a bias in the data. For example if depressed people were less likely to complete follow-up questionnaires, the average for the follow-up questionnaires would show fewer symptoms of depression than the average for the initial questionnaires.

The authors do not discuss whether the people who did not complete the questionnaires after hormone therapy were significantly different from those who did.

Leaving suicide out of the results

The person who committed suicide was not included in the study; if they had been it might have distorted the data. Presumably their responses at baseline would have increased the average score for symptoms of depression, but without a follow-up questionnaire for them, symptoms of depression would appear to go down. Leaving them out makes the results clear – symptoms of depression went down among everyone else.

At the same time, without data on the person who committed suicide during follow-up, it is not fully accurate to say that symptoms of depression went down after treatment. For at least one person it doesn’t make sense to talk about symptoms of depression going down.

Suicide during follow-up is part of the results of this study. It is relevant to the question of whether or not people felt better after transition. When someone commits suicide during a study, this needs to be part of the discussion. When did they commit suicide? Were they depressed before transition? Did they regret the surgery? Did they say they were depressed during or after transition?

Not talking about the suicide is disrespectful to the person who died. It leads to possibly false conclusions about the effects of transition. And it stops us from being able to figure out what we can do to prevent future suicides – do we need to give people more therapy before medical treatments? should some people not get surgery? do we need to give people more therapy after surgery?

Back to the questions raised by the study

What can we do to reduce suicide, suicide attempts, and suicidal thoughts in transgender people who have transitioned?

Clearly, medical transition is not enough. It does not prevent suicide, suicide attempts, or suicidal thoughts. It does not even reduce the prevalence of suicide attempts.

As far as I know, this is the only study that has followed a group of people with gender dysphoria during treatment and collected data on suicide attempts.

We need more research to figure out how to prevent suicide and suicide attempts among transgender people after transition. It might also help if we knew more about what was going on in this study.

When exactly were the suicide attempts – after hormones or after surgery? When exactly did the person commit suicide? Does this reflect regret related to the surgery itself or something else?

Were there any gender differences in the suicide attempts?

Were there any differences in the specific treatments given to the people who attempted suicide? Were there any problems in the outcomes of the treatments?

Did the same people attempt suicide before and after transition?

Did the people who attempted suicide say they were depressed? Had they been diagnosed with mental health issues? Were they getting counseling?

Do we know of things that went wrong in the lives of the people who attempted suicide?

Do some people need more counseling and evaluation before transition? Should we adapt the hormonal doses or surgeries for different people? Do we need to give additional support after transition? Are there alternatives to transition that would better help some people deal with gender dysphoria?

At this point all we know is that we can not rely on medical transition to prevent or reduce suicide attempts among transgender people.

We need to know more.

Why didn’t the percentage of suicide attempts go down when people were reporting fewer symptoms of depression?

The results of this study are somewhat confusing. People reported that their symptoms of depression and psychological distress went down after transition. In addition, the vast majority of people who had transitioned said that they felt better – they were happier (93%), less anxious (81%), more self-confident (79%), and their body-related experience improved (98%). Only 2 people said they were more anxious and 1 less self-confident. Only 2 said that their overall mood was similar.

So why did 7 people (17.6%) report that they had suicidal thoughts? Why were there 4 suicide attempts?

Were the people who had suicidal thoughts so unhappy to start with that an improvement in their mood still left them suicidal? Perhaps they had even more suicidal thoughts before transition – but the prevalence of suicide attempts was not affected by transition.

It’s possible that the group’s average scores for depression are in the normal range while a few individuals are miserable. On the other hand, the group has an above average number of suicide attempts and suicidal thoughts. According to an Emory University website“It is estimated that 3.7% of the U.S. population (8.3 million people) had thoughts of suicide in the past year, with 1.0% of the population (2.3 million people) developing a suicide plan and 0.5% (1 million people) attempting suicide.” In this study, 17.6% of the group reported suicidal thoughts at the moment of follow-up. The suicide attempt percentage was 9.8% at follow-up.

We are looking at a group of people with elevated levels of suicidal thoughts and suicide attempts – how does that fit with questionnaires that find a normal level of symptoms of depression?

Are we seeing accurate reports of how people feel? Are people minimizing their problems when they fill out questionnaires after treatment?

The authors of the study do not discuss the apparent contradiction between suicide attempts and suicidal thoughts one the one hand and an improved mood on the other.

The authors do point out that the percentage of suicide attempts at the beginning of the study was lower than in other studies of transgender people. It may be that the participants in this study had fewer problems than most transgender people; for one thing they are a group that is able to access medical care. However, that does not answer the question of why for this particular group of people transition did not change the prevalence of suicide attempts.

We need more research into what is going on here. We need to be able to identify people who may attempt suicide or feel suicidal after transition so we can help them.

Why didn’t surgery improve the mental well-being of the patients?

We don’t know and we need more research to answer this question. However, here are a few possibilities:

Possibility #1 – Return to regular life

In their discussion, the authors suggest that there might be an initial euphoria after beginning hormones that wears off later on. In addition, after surgery, people might be “again confronted with stigma and other burdens.”

In other words, the improvement after hormone therapy is higher than the improvement will be in the end. There is still an improvement later on, but the initial level of euphoria isn’t going to last. If this is true, it would be important information for people who are transitioning so that they don’t have false expectations of what life will be like after transition is complete.

Possibility #2 – Surgery is not the best treatment for everyone

The authors also suggest that further studies should look at exploring the idea that some patients might want hormones without surgery.

It may be that surgery is not the best treatment for everyone with gender dysphoria. Perhaps some people would have been better off with just hormone therapy.

Previous studies have found that about 3% of people who have had genital surgery regret it, so we would expect one or two people out of 50 to regret their surgery. Perhaps they are depressed and this affects the group average.

Possiblity #3 – Effects of surgery

It is also possible that some people had post-surgical depression and that this affected the results.

Perhaps some people were still recovering from surgery and did not feel well (the study included people 1 to 12 months after surgery). In particular, this might lead to the increase in sleeping problems found in the study.

Perhaps some people were dealing with complications of surgery.

Perhaps the hormonal changes after surgery affected people’s moods.

Possibility #4 – People were already happy

On the other hand, perhaps by the time people get surgery, they are already happy due to counseling, hormones, and social transition.

Perhaps if people had been forced to stop with hormone therapy alone, they would have become unhappy. As the authors point out, it may have made a difference that they knew they were going to be able to get surgery.

Possibility #5 – Surgery doesn’t affect mental health

It may simply be that surgery does not improve mental health. At this point, we do not have proof that it does.

In the end, we just don’t know.

Further studies are needed to determine if surgery is helpful and who should get it. Perhaps the authors of this study can use the data they already have to address this question.

The authors talk about the prevalence of suicide attempts before and after transition, but they don’t talk about the time periods they are looking at. The authors say that the prevalence of suicide attempts was unchanged, but they don’t explain when the suicide attempts took place before treatment. It makes a big difference if they are comparing three years before transition to three years afterward or if they are comparing a lifetime before transition to the average 3 year follow-up period – a follow-up that took place 1-12 months after surgery.

In addition, the actual data on suicide attempts is confusing. In Table 3, the authors list the prevalence of suicide attempts as 9.4% at presentation and 9.3% at follow-up. However, in their discussion they say the suicide attempt percentages were 10.9% initially and 9.8% at follow-up.

Looking at Table 3, there were 5 attempts in a group of 54 people which would give a percentage of 9.26%, a number that doesn’t match either of the ones given by the authors. In addition, there were 4 attempts in a group of 42 people which would give 9.52%, another number that doesn’t match.

The percentage they gave at baseline in Table 3 seems to be 5 out of 53 people, while the percentage at follow-up seems to be 4 out of 43. Perhaps one of the 54 people didn’t answer the question on suicide attempts in the first set of questionnaires. But where does the additional person come from in the second set of questionnaires? If they are including the person who committed suicide in the suicide attempts, wouldn’t the number of people used to calculate the percentage before treatment be 54 or 55, not 53?

None of this explains why they would list different numbers in their discussion. Perhaps there were some suicide attempts by the same person that were included in one set of numbers but not the others? The table talks about the prevalence of suicide attempts while the discussion talks about the percentage.

This is a somewhat surprising case report of a trans man (born female) who developed anorexia nervosa after sex reassignment surgery.

The 24-year-old patient had surgery to remove his breasts, ovaries, and uterus. Afterwards he began binging and purging. He had not had problems with eating behaviors or weight loss before surgery.

This case is similar to the trans woman (born male) in this study who began to diet excessively after sex reassignment surgery. It is, however, different from this trans man who stopped dieting once he was on hormones and menstruation ceased.

The authors suggest that the eating disorder is an “expression of a gender identity process, or a conflict of an acceptance of one’s own sexuality.”

It is easy to understand why someone with gender dysphoria might dislike their body and develop problems eating, but in this case, the patient had already changed his body.

Why did the eating disorder develop after physical transition was complete?

Had he been focused on changing his body with hormones and surgery and then when he was done, he focused on his shape?

Was his eating disorder a sign of persistent body dissatisfaction no matter what he did?

The authors suggest that the patient’s underlying problems may have caused the eating disorder:

“In this case, there was clearly a linkage between a lack of sense in self-efficacy and a body dissatisfaction that continued after the sex change surgery. Discomfort with her/his own body appeared to be more deeply anchored than just being rooted in the wish to change the physical appearance.”

Alternatively, might the surgery have caused an abrupt shift in hormones that led to an eating disorder? More importantly, could adjusting his hormones help him recover from the eating disorder?

We think of testosterone and estrogen as sex hormones, but they are much more than that. Like all hormones, they are part of a complex system of chemicals that affect each other. Specifically, we know that “sex” hormones also play a role in appetite.

“The sex hormones estrogen, progesterone and androgens are involved in the complex regulation of appetite, eating and energy metabolism. In most species, including man, food intake and reproductive functions are closely linked. Thus, during the different hormonal phases of the menstrual cycle daily food intake varies and, moreover, remarkable physiological adaptations of appetite and body composition occur during pregnancy and lactation. In addition, regulation of eating behaviour and metabolic functions by sex hormones is of considerable general importance for women’s health, as indicated by the disturbances in this regulation associated with a number of clinical disorders.”

In this case study, the patient’s estrogen levels would have dropped significantly after his ovaries were removed. In addition, doctors normally reduce the dose of testosterone after surgery, although to a level typical for a man.

Women eat less during the phase of the menstrual cycle when estrogen levels are high, so it is possible that a drop in estrogen levels would be connected to eating more.

Furthermore, bulimia may be connected with polycystic ovary syndrome (PCOS), a syndrome which is characterized by elevated androgen levels.

Testosterone stimulates appetite and high circulating levels of this androgen in women have been associated with impaired impulse control, irritability and depression, i.e., common features of women with bulimia. Accordingly, it has been proposed that elevated levels of androgens may promote bulimic behaviour by influencing craving for food and/or impulse control. Hypothetically, bulimia may, in some cases, have a hormonal, rather than a psychiatric etiology, a suggestion supported by the observation that antiandrogenic treatment reduces bulimic behaviour. This may turn out to be a novel and valuable approach to treating women with BN, particularly those with hyperandrogenic symptoms.

The patient in this case study had symptoms that are typical of bulimia, binging and purging. Perhaps in his case the bulimia was related to the sudden drop in estrogen after surgery coupled with male levels of testosterone.

Most people do not develop eating disorders after sex reassignment surgery. There would have to be other factors involved, possibly genetic or psychological.

We have very little data on eating disorders and gender dysphoria, just a set of case studies.

However, we now have two cases of trans people developing an eating disorder after having surgeries that would have changed their hormones.

In one case, a trans woman began restricting her eating after surgery; in her case the surgery would have decreased her testosterone levels and thus, possibly decreased her appetite.

In this case, a trans man began binging and purging after surgery which would have decreased his estrogen levels and thus, possibly increased his appetite.

We need more research into this question. Do changes in hormones trigger eating disorders in some trans people? Most of all, can we use this to find a way to help trans people with eating disorders?

The patient also had problems with alcohol and drug abuse, self-mutilation, and suicide attempts, but these had begun at age 17. He was diagnosed with “gender identity disorder, alcohol dependence, anorexia nervosa (purging subtype), major depression (Axis I), and borderline personality disorder (Axis II).

The patient’s father had obsessive-compulsive disorder and one of his sisters had an affective disorder.

As a child, the patient felt like a boy, didn’t play with girls, tried to hide any feminine parts of his silhouette, and hated feminine features of his body.

This is a fairly straightforward case study of a Turkish trans man (born female) with anorexia. In order to avoid menstruating, he dieted excessively and induced vomiting. He also wished to avoid looking female. This went on for 21 years, beginning when he was 19.

Once he was on hormones and menstruation stopped, the disordered eating ended. It has not returned after two years. He says he is no longer concerned with his weight since he is living as a man.

It is important to remember that this is just a case study. This is only one individual; the relationship between eating disorders and gender dysphoria is complicated. We can only come to limited conclusions from any one person’s story.

In fact, there are six other case studies where physical transition did not cure an eating disorder. Two trans women with eating disorders were already on hormones (here and here), although one of them does not seem to have been interested in recovering from her disordered eating. One trans woman believed that transition had cured her, but she was severely underweight, even more so than she had been before transition.

There are three case studies where surgery seems to have caused or triggered disordered eating. This trans man began binging and purging for the first time after having his breasts, uterus, and ovaries removed. One of the trans women in this study had an eating disorder in adolescence; her symptoms returned after sex reassignment surgery 20 years later. Finally, this adolescent trans man recovered from an eating disorder and transitioned; after his mastectomy, he began to relapse and ten months later he returned to the clinic for eating disorders.

In addition, there are a number of case studies where factors other than gender dysphoria played a role in an eating disorder. The most striking is this case of identical twins; both twins had anorexia, but only one had gender dysphoria. The twins shared genes and an abusive father, but one grew up to be a feminine gay man while the other was a trans woman.

Back to this case study. It is clearly different from typical cases of anorexia:

“The rejection of femininity was the primary underlying motivation for loss of weight, and not the wish to look slim. She stated that her primary motive for purging was to stop menstruation and her second motivation was to get rid of female body shape; the latter motivation was so strong that she expressed that if she could look like a man if she put on weight she would eagerly try to put on some weight. Thus with this definite statement she was to be separated from the primary cognition of AN which is an intense fear of gaining weight. Her eating disorder symptoms were greatly alleviated after sex reassignment.”

More importantly, in this case, taking testosterone stopped the disordered eating.

The trans man in this story also had a sex reassignment surgery, although the study does not say what the surgery was (mastectomy, genital surgery, or hysterectomy with removal of the ovaries). He changed his name and is living as a man.

It is likely that transitioning cured him of anorexia. However, it is also possible that the testosterone itself played a role. Low testosterone is linked to eating disorders in both men and women. There is a study underway to see if taking testosterone can help women with eating disorders, but we will not know the results for a few more months.

A few other things of note:

The patient did not seek help for his eating disorder, even when he saw a psychiatrist for depression. His eating disorder only came out when he applied to change his sex on his identity card and was referred to a psychiatry clinic.

In order to be able to take hormones, the patient stopped vomiting. However, he continued to restrict his calories until he was actually on hormones.

Before treatment, the trans man ate more when he was depressed.

He had problems with his teeth due to vomiting eroding the enamel.

After finishing college, he had a serious suicide attempt.

The patient’s gender dysphoria began in childhood:

“In her early childhood A.T, felt strongly that she belonged to the male sex. She played boys’ toys and games, preferred boys for playmates, and she was interested in football. When she reached puberty the growth of her breasts and the onset of menstruation caused her to have severe stress, in order to hide her breasts she was wearing extra large size clothes and she was pretending a kyphosis-like posture. During the first year of her university education she had severe depressive symptoms connected with her gender dysphoria; she was spending the greater part of her time at home as she was uneager to dress and live like a woman.”

This article is a report on health care provided to youth with gender dysphoria at a clinic in British Colombia, Canada. I’m going to focus on just the demographics in this post and do another post later.

Most of their patients were trans men (born female). This is similar to the current situation at other clinics for teenagers, but different from the past at other clinics. It is also different from most European clinics for adults.

Their patients had other psychiatric diagnoses including mood disorders, anxiety disorders, and eating disorders. The patients in this study had more psychiatric problems than teenagers studied at a clinic in the Netherlands.

Suicide attempts are a serious problem among their patients. 12% of their patients had attempted suicide before coming to the clinic; 5% attempted suicide after their first visit to the clinic. The decrease is encouraging, but clearly we need to do more to help patients during and after transition.

Some of their patients had to be hospitalized for psychiatric problems. 12% of their patients had been hospitalized before coming to the clinic, but only 1% were hospitalized after the first visit. Again, we need to be sure to provide support during and after transition.

THE INCREASE IN TEENAGE PATIENTS

The clinic has seen a fairly dramatic increase in the number of teenage patients from 2006-2011. They went from fewer than 5 cases/year before 2006 to nearly 30 cases in 2011.

Number of new patients with gender dysphoria seen in 1998-2011. MtF, black bars; FtM, hatched rectangles.

Unlike the other two studies, the majority of the patients at this clinic were always trans men (born female). In fact, before 2006 almost all of the patients were trans men. After 2006, the number of trans women patients (born male) began to increase. However, trans men still made up 54% of all the patients they saw between January 1998-December 2011.

This is different from the pattern found in the clinics in Toronto and Amsterdam. In those two clinics the patients were mostly trans women before 2006, but after 2006 they were mostly trans men.

It’s hard to know what these numbers mean because we don’t know how common gender dysphoria is among teenagers.

“The prevalence of adolescent-onset gender dysphoria is not known, and there are limited accurate assessments of prevalence of transgenderism in adults in North America. However, the prevalence of adults seeking hormonal or surgical treatment for gender dysphoria is reported to be 1:11 900 to 1:30 400 in the Netherlands.”

Does this increase reflect an increase in the number of teenagers with gender dysphoria? If so, why are the numbers increasing?

Alternatively, is this increase due to people with gender dsyphoria seeking physical transition at a younger age?

Statistics on most European clinics have shown many more trans women transitioning than trans men (the pattern is reversed in Japan and Poland). Now the statistics on Canadian and Dutch teenagers show more trans men transitioning than trans women.

Are there more trans men than in the past? If so, why?

Or are trans men transitioning at a younger age than trans women? But then why did the other two clinics treat more teenage trans women than teenage trans men in the past?

BASIC DEMOGRAPHICS OF THE PATIENTS IN THIS STUDY

The clinic at British Colombia Children’s Hospital saw 84 youth with a diagnosis of gender dysphoria from January, 1998 to December, 2011.

45 of the patients were trans men, 37 were trans women, and 2 were males who weren’t sure of their gender identity.

Two of the trans women had disorders of sex development – one had Klinefelter syndrome (XXY chromosomes) and one had mild partial androgen insensitivity syndrome (i.e. her body made androgens, but they didn’t fully affect her).

The median age at the first visit was 16.8, the range in ages was from 11.4 to 22.5.

At the first clinic visit, most patients were in school grades 8-10 (32%) or grades 11-12 (48%); 12% were in grades 5-7, and the remaining 8% were in college/university or no longer attending school.*

PSYCHIATRIC COMORBIDITIES

Diagnoses made by a mental health professional:**

35% of the patients had a mood disorder (20 trans men, 7 trans women and probably the two males with uncertain gender identity)

24% had an anxiety disorder (15 trans men, 4 trans women and probably one male with an uncertain gender identity)

26% of their patients had two or more mental health diagnoses (12 trans men, 9 trans women) and probably one male with an uncertain gender identity.

Suicide attempts:

10 of the teenagers attempted suicide before coming to the clinic (12%). 6 of them were trans men and 2 were trans women. Perhaps the other two were the two males who weren’t sure of their gender identity.

4 of the patients attempted suicide after the first visit to the clinic (5%). Three of them were trans men and one was a trans woman.

Psychiatric hospitalizations:

12% of the patients had been hospitalized for a psychiatric condition before coming to the clinic – seven trans men and three trans women.

One trans man was hospitalized for a psychiatric condition after the first visit to the clinic (1%).

One trans woman and one trans man discontinued the use of a puberty blocker after they developed emotional lability (7% of the patients who took the puberty blocker). The trans man also had mood swings.***

One trans man had significant mood swings as a side effect of testosterone treatment. (3% of the patients who took testosterone.)

Two trans men temporarily stopped testosterone treatment due to psychiatric conditions – one was depressed and one had an eating disorder. (5% of the patients who took testosterone.)

One trans man temporarily stopped testosterone treatment due to distress over hair loss. (3% of the patients who took testosterone.)

Gender differences:

Trans men were significantly more likely to have depression or anxiety disorders than trans women. 44% of trans men had mood disorders compared to 19% of trans women. 33% of trans men had anxiety disorders compared to 11% of trans women.

There were no significant gender differences in other mental health issues.

27% of trans men had two or more psychiatric diagnoses compared to 24% of trans women. This seems surprising given that trans men were more likely to have mood and anxiety disorders.

The most important issue is the number of suicide attempts.

Why were there four suicide attempts after the first visit to the clinic?

Were the suicide attempts related to the two patients who developed emotional lability on blockers? or the trans man who developed mood swings after taking testosterone?

Were they related to the trans man who stopped taking hormones due to depression? Was he the same person as the trans man who developed mood swings on testosterone?

What about the trans man who stopped his hormones due to an eating disorder?

When were the suicide attempts? Were they before the patients got blockers or hormones? Did they happen after stopping hormones for any reason? Or were the patients already on hormones or blockers?

Could they have been prevented by more therapeutic support before treatment? during treatment?

Is there a way to identify which patients are at risk for suicide attempts during or after treatment?

It is encouraging to see that there were fewer suicide attempts after the first visit to the clinic than before, but it is not enough. We need to do more.

We also need more data on the decrease in the number of suicide attempts after coming to the clinic. Was it statistically significant? Was the time period before the first visit to the clinic equal to the time period after the first visit to the clinic?

Psychiatric comorbidities comparison

Compared to a clinic in the Netherlands, these patients were more likely to have mood disorders (35% vs. 12%), but about as likely to have anxiety disorders (24% vs 21%).

5% of the Vancouver patients had an eating disorder while none of the patients in the Dutch study did.

7% of the patients in this study had a substance abuse problem while only 1% of the patients in the Dutch study did.

26% of the patients in this study had two or more psychiatric diagnoses. In comparison, only 15% of the teenagers in the Dutch study had two or more psychiatric disorders.

Finally, the Dutch study found that trans women were at higher risk for having a mood disorder or social phobia while this study found that trans men were at higher risk for mood and anxiety disorders.

Why is the psychiatric comorbidity higher in the Vancouver patients?

The authors of the report suggest that it might be because the average age of their group was higher than the average age in the Dutch study – 16.6 year vs 14.6 years. It might simply be that older teenagers have had more time to develop mental health issues.

They also suggest that there could be differences in diagnostic criteria. Both groups seem to have been using DSM-IV diagnoses, but the Vancouver data was based on clinic notes while the Dutch data was based on interviewing parents. It may be that parents underestimate their children’s problems. For example, they might not realize that their teenager has a substance abuse problem or an eating disorder.

In addition, the Vancouver study includes all 84 patients their clinic saw between 1998-2011. In contrast the Dutch group invited 166 parents to participate in their study, but only 105 parents did so. It is possible that the 61 parents who did not participate had children with more problems, although the authors suggest that the inconvenience of travelling to the center was the main issue.

Finally, the Dutch group has 17 teenagers who were referred to the clinic but dropped out after just one session, “mostly because it had become evident that gender dysphoria was not the main problem.” These patients might have had more psychological comorbidity than others.

It is hard to compare this to the Vancouver clinic, however, because the Vancouver clinic’s focus is on endocrine care. 93% of the patients they saw had already been diagnosed with gender dysphoria by a mental health professional. Were there teenagers in Canada who discovered that gender dysphoria was not the main problem and did not go on to the clinic? If so we would expect the two clinics to have similar rates or psychological comorbidity. If not, we might expect a higher rate of comorbidity in Canada.

A final possibility is that the Canadian teenagers with gender dysphoria simply have more psychological problems than Dutch teenagers with gender dysphoria. Perhaps they experience more bullying and violence. Perhaps they had less supportive parents.

As usual, we need more studies. Why are the numbers of teenagers at clinics for gender dysphoria increasing? What is the prevalence of gender dysphoria among teenagers? How common are psychological comorbidities? Are trans men or trans women more at risk for depression and anxiety? What can we do to prevent suicide attempts after treatment begins? How can we better support patients with gender dysphoria during and after transition?

*This would suggest that 48% of the students were 16-17 years old, 32% were 13-15, 12% were 11-12, and 8% were 18-22.5.

** The table indicates that these were diagnoses made by a psychiatrist or psychologist. There were other diagnoses the authors didn’t include in the table: 1 patient with trichotillomania, 2 with borderline personality disorder, 1 with psychosis not otherwise specified, 1 with adjustment disorder, 2 with tic disorders, and 1 with oppositional-defiant disorder. I am not sure why these diagnoses weren’t included; perhaps they weren’t made by mental health professionals.

***The blockers being used were gonadotropin-releasing hormone analog or GnRHa.

Twin and family studies suggest that there may be a genetic component to gender dysphoria. Researchers have naturally been trying to find genes linked to gender dysphoria.

Most of the research has focused on genes that are known to be related to sex hormones in some way.

I. Researchers may have found genes related to gender dysphoria in trans men (born female).

A large Spanish study found an association between the gene for Estrogen Receptor β and gender dysphoria, but a medium-sized Japanese study did not.

A small Austrian study found an association between gender dysphoria and a different gene related to converting progesterone into androgens. Nobody else has looked at this gene.

A possible flaw with the Austrian study is that the control females were seeking help with perimenopausal issues; it may be that their genes were different from the general public.

Both of these results need to be replicated.

It is also possible that the genes were related to sexual orientation.

In the Spanish study, all of the trans men were attracted to women; it is likely that 95% of the control women were attracted to men.

The Austrian study does not talk about sexual orientation, but typically most trans men are attracted to women and most women are not.

Many control women also had the genetic variations found in trans men. Some other genes or environmental factors must also be involved.

These results need to be replicated. The Austrian study was relatively small and possibly flawed while the Spanish and Japanese studies contradict each other.

II. Researchers thought they had found genes related to gender dysphoria in trans women (born male), but larger studies did not replicate the results. It is possible, however, that the genes related to gender dysphoria are different in different populations.

None of the studies found a relationship between gender dysphoria and the gene for CYP19A1.

Three studies found no difference in the gene for estrogen receptor β; the study that found a difference was much smaller than the others.

Three studies found no difference in the gene for androgen receptor, including one study of over 400 trans women.

III. An Italian study that looked at the Y chromosome found no differences between trans women and control males.

IV. An Austrian study that looked at sex chromosomes in trans women and trans men found no significant abnormalities.

V. A Japanese study that looked at genes related to estrogen receptor alpha and progesterone receptor found no differences between the genes of male to female transsexuals and male controls or the genes of female to male transsexuals and female controls. This study also looked at estrogen receptor β, androgen receptor, and CYP19A1 and found no differences for those genes either; this is one of the studies discussed above.

VI. An Austrian study of a gene related to steroid 5-alpha reductase (SRD5A2) found no differences between trans women, trans men, and male and female controls. SRD5A2 is involved in the conversion of testosterone to dihydrotestosterone.

It is important to remember that there may be some other genetic variations that are linked to gender dysphoria in trans women, something that we haven’t studied yet.

At this point, however, we do not seem to have found genes related to gender dysphoria in trans women.

Recommendations for future research:

Look at genes other than the ones related to sex hormones or sex chromosomes. Perhaps the cause of gender dysphoria is different from what we expect.

Control for sexual orientation by including some cis lesbians and gay men in the study.

Study trans people with African ancestry – and other groups that have not yet been studied. Studies so far have looked at people from Spain, Italy, Japan, Austria, America and Australia (Caucasian only), and Sweden.

They found no connection between the genes related to androgen receptors or aromatase, but they did find an association between the ERβ gene and gender dysphoria in trans men.

“The repeat numbers in ERβ were significantly higher in FtMs than in control group, and the likelihood of developing transsexualism was higher (odds ratio: 2.001 [1.15-3.46]) in the subjects with the genotype homozygous for long alleles.”

Three caveats:

All the trans men participating in the study had gender dysphoria that began before puberty and were attracted to women (i.e. members of their biological sex). The control females were probably 95% straight. It is possible that the genetic difference they found is related to sexual orientation, not gender identity.

This is not an absolute difference, it is a difference in frequency – 69% of the trans men had the long allele for ERβ, but so did 59% of the control women. Some other genes or environmental factors must also be involved in gender dysphoria (or sexual orientation).

The study below found different results; however, this study was larger.

They found no differences between the genes of male to female transsexuals and male controls or the genes of female to male transsexuals and female controls.

“The present findings do not provide any evidence that genetic variants of sex hormone-related genes confer individual susceptibility to MTF or FTM transsexualism.”

The abstract does not provide any information on the demographics of the trans women and trans men.

The results of this study for ERβ contradict the results of the Spanish study. The Spanish study looked at 273 trans men while this study only looked at 74, so it is unlikely that the Spanish study is simply wrong.

It may be, however, that this study is still right, at least in Japan. People in different countries have different genes; they may have different genes for gender dysphoria.

It is possible that cultural differences or medical policies may mean that clinics in different countries are looking at groups of people with different problems.

Finally, gender dysphoria might be caused by different factors or combinations of factors in different cultures. Japanese trans men may be different from Spanish trans men in some important way.

A possible flaw in this study is that the females controls were women seeking help with perimenopausal disorders; they may have had genes that were different from the general population. The male controls, on the other hand, were “participating in a health prevention program.”

Since the results found that the frequency of a particular mutation was different in female controls from all of the other groups, it matters a great deal if the control females are significantly different in some other way from the other participants.

This study looked at a different gene from the other studies, CYP17. CYP17 encodes cytochrome, an enzyme involved in converting progesterone and pregnenolone into androgens.

The authors found that a particular mutation of this gene, CYP17 −34 T>C, was associated with female to male transsexualism, but not male to female transsexualism.

They also found that, “the CYP17 −34 T>C allele distribution was gender-specific among controls. The MtF transsexuals had an allele distribution equivalent to male controls, whereas the FtM transsexuals did not follow the gender-specific allele distribution of female controls but rather had an allele distribution equivalent to MtF transsexuals and male controls.”

In other words, trans men and trans women were similar to male controls and not female controls.

They point out, however, that there were women without gender dysphoria who had the mutant allele as well as women with gender dysphoria who did not have it. “Thus, carriage of the mutant CYP17 T−34C SNP C allele is neither necessary nor sufficient for developing transsexualism.”

In other words, there must be other genetic or environmental factors involved.

They do not discuss the sexual orientation of the participants in the study. As discussed above, it is possible that most of the trans men were attracted to women and that this genetic mutation is related to sexual orientation, not gender identity.*

Finally, I keep coming back to the female control group. What if converting progesterone to androgens is related in some way to perimenopausal symptoms? What if the mutant gene protects against problems in menopause somehow and so the female control group includes fewer people with this gene?

2007:

A common polymorphism of the SRD5A2 gene and transsexualism. This Austrian study compared 100 trans women, 47 trans men, 755 control men, and 915 control women. They looked at a mutation of the steroid 5-alpha reductase gene (SRD5A2); this gene produces an enzyme that catalyzes the conversion of testosterone to dihydrotestosterone.

They found no differences between any of the groups. The mutant allele was not associated with transsexualism and its distribution was not gender specific among controls.

This study has the same flaw as the 2008 study listed above; the control females were all seeking help for problems with perimenopause.

2002:

Sex chromosome aberrations and transsexualism. This Austrian study looked at the chromosomes of 30 trans women and 31 trans men. They did not find significant abnormalities, although they suggested further investigation might be worthwhile.

“We could not detect any chromosomal aberrations with the exception of one balanced translocation 46,XY,t(6;17)(p21.3;q23). Importantly, no sex chromosomal aberrations, which would be detectable on the G-banded chromosome level, have been observed.”

They conclude:

“The data described here provide evidence that genetic aberrations detectable on the chromosome level are not significantly associated with transsexualism. In addition, molecular-cytogenetic FISH analyses did not reveal deletions of the androgen receptor gene locus on chromosome Xq12 or of the SRY locus on chromosome Yp11.3. Multiplex PCR analyses demonstrated one AZF deletion in a male-to-female transsexual.”

but:

“However, the detection of one carrier of a Y chromosome microdeletion out of 30 male-to-female transsexuals could argue for further investigations. This is of special interest in light of the recent discussion of gamete banking before hormonal and sex reassignment surgery of transsexuals.”

“This gender disorder does not seem to be associated with any molecular mutations of some of the main genes involved in sexual differentiation.”

The trans women were aged 24-39 and had already begun hormone therapy. A little over half of them had already had sex reassignment surgery and the rest were waiting for it.

2002:

Sex chromosome aberrations and transsexualism. This Austrian study looked at the chromosomes of 30 trans women and 31 trans men. They did not find significant abnormalities, although they suggested further investigation might be worthwhile.

Interestingly, 98% of the trans women had chromosomes that were 46,XY, i.e. normal, but 2% of the group showed aneuploidy, or abnormal chromosomal numbers. This is slightly higher than usual.

The abstract does not go into detail, but presumably the aneuploidies were cases of Klinefelter syndrome; a condition where a person typically has one Y chromosome and two X chromosomes. Most people with Klinefelter’s syndrome identify as male, but there may be a higher than usual occurrence of gender dysphoria among people with Klinefelter’s.

There are no details on the trans women in the abstract; however, the same researchers did a very similar study of trans men (see above). It may be that the participants in the two studies were screened in the same way.

This Australian and American study compared 112 male to female transsexuals to 258 control males. They looked at genes for androgen receptor, estrogen receptor beta, and aromatase. No differences were found for the estrogen receptor or aromatase, but transsexuals had longer repeat lengths for the androgen receptor allele.

This result was not found in the Spanish study or the Japanese study above. The Spanish study was larger than this one. Thus, this result has not been replicated.

However, it is possible that this genetic variation is connected to gender dysphoria for Caucasian trans women in America and Australia, but not in Spain or Sweden and not for Japanese trans women.

It is also possible that the genetic difference found here is related to sexual orientation, not gender identity. The researchers in this study only knew the sexual orientation for about 40% of the participants in the study, but people with gender dysphoria are much more likely to be attracted to people of the same biological sex than people without gender dysphoria.

As in the Spanish, study above, this is not an absolute difference, it is a relative one. There were also cis men who had long AR repeat lengths (Figure 1). Again, some other genes or environmental factors must also be involved in gender dysphoria (or sexual orientation).

The trans women in this study were all Caucasian; 76 of them were from an Australian clinic and 36 of them were from UCLA in America. Almost all of them were on hormones. Some of them had gender dysphoria in childhood. “The sexuality is only known for approximately 40% of patients, because some patients did not wish to discuss or disclose this information or the patient’s sexuality was flexible and not easily classified.”

This Swedish study compared the genes of 24 male to female transsexuals and 229 male controls. They looked at specific areas in the androgen receptor gene, the aromatase gene, and the estrogen receptor β gene.

They did not find a difference between male-to-female transsexuals and men for the first two genes, but they did find a difference related to the gene for estrogen receptor β. “Transsexuals differed from controls with respect to the mean length of the ERβ repeat polymorphism.”

In addition, “binary logistic regression analysis revealed significant partial effects for all three polymorphisms, as well as for the interaction between the AR and aromatase gene polymorphisms, on the risk of developing transsexualism.”

The study was very small, however, and as the authors said, “results should be interpreted with the utmost caution.”

The three more recent studies above did not replicate the findings of this study. The other studies were much larger than this one, so it is possible that these results were a fluke.

It is also possible, that the genes linked to gender dysphoria in Sweden are different from the genes linked to it in other countries.

The authors of the American-Australian study described above say, “Our sample size was approximately four times larger than that of the Swedish study, so it is possible that the former study was underpowered to detect a false positive. Alternatively, there might be differences between Swedish and non-Swedish populations in this polymorphism. In the Swedish study, the long repeat occurred in 51.8% of control subjects and 67.1% of transsexuals, whereas in the present study the long repeat occurred in 36.5% of control subjects and 44.1% of transsexuals. Thus, although there was a trend in the same direction in both studies, there are major differences in prevalence of these long repeats between the two populations.”

The only data we have on the participants in the study are that the trans women were Caucasian and the vast majority of the controls were also Caucasian. Again, it is likely that there was a higher percentage of people attracted to male in the group of trans women than the general population; this might have affected the results.

As the authors point out, “the gene variants investigated in this study are relatively common, none of the studied variants could hence be assumed to be the primary cause of this condition.” Rather, genes might increase or decrease the chance of developing gender dysphoria.

So, if the results of this study are not a fluke, we are still left with the questions of what other factors contribute to developing gender dysphoria and is this a gene related to gender dysphoria or sexual orientation in Sweden?

The end result of all this:

We have a couple of possible candidates for genetic variations related to gender dysphoria in trans men, but we need further studies. We need to replicate the results and to control for sexual orientation. In the case of the CYP 17 gene, we need to compare trans men to healthy control females instead of women with perimenopausal issues.

We don’t have any strong candidates for genetic variations related to gender dysphoria in trans women. Future studies might do well to look for genes that are not related to sex hormones. As always, they should control for sexual identity. (This should be done by adding lesbians and gay men without gender dysphoria, not by excluding trans women who are attracted to women from the studies. See my rants in articles on brain sex.)

*A group of trans women would include many more people attracted to men than a group of control males, but typically about half of trans women are attracted to women while most trans men are attracted to women. Thus this could be a comparison of two groups (control males and trans men) where a large majority of the people are sexually attracted to women, one group where half the people are attracted to women (trans women), and a group where about 5% of the people are attracted to women (control females).

This study found that trans women (born male) and control males responded to estradiol in the same way. Specifically, they looked at how taking estradiol affected the levels of other hormones: testosterone, estradiol, lutenizing hormone, and follicle stimulating hormone.

The authors were attempting to test Dorner’s theory that gender dysphoria in trans women is caused by a defect in a normal imprinting mechanism of testicular testosterone on the hypothalmus. In other words, it might be that testosterone affects the hypothalmus prenatally, but something goes wrong with the process in trans women.

They conclude that if there is such a defect, it does not affect the levels of these hormones or the way they response to estrogen.

The study does not, of course, prove Dorner’s theory.

What I found interesting was that both trans women and control men responded to taking estrogen in the same way.

This is a study about rats. As always, we don’t know if what works for them is true of humans. The study does, however, point to an important factor to consider in any research on gender identity.

The authors found that they could completely change an observed sex difference in adult rats’ brains by changing their sex hormones. Earlier exposure to sex hormones made no difference.

This means that this observed sex difference was completely caused by adult circulating androgens.

The authors suggest that this might also happen in human brains. They refer to studies of the structures in transsexual brains and suggest that we can’t be sure that observed differences were caused by differences in the early development of the brain. They might have been caused by taking cross-sex hormones.

This study is from 1999, so they are referring to some of the early work on gender identity and the brain by Swaab et al and Zhou et al. Those studies included the brains of trans people who had been taking hormones.

This study of hormones in adult rat brains would not affect studies if they a) look at trans people who have not yet taken any hormones and b) test people to make sure their hormonal levels are in the normal range for their biological sex.*

It is also possible that some areas of the brain are controlled by circulating hormones and some are affected by earlier exposure to hormones as well as circulating hormones. The authors cite examples where castration dramatically changed areas of the rat brain, but did not completely reverse the sex difference.

The authors also discuss studies that found you could change a bird’s brain by changing its hormones.

They conclude by discussing the ways adult hormones affect the human brain.

“Human behavior is also subject to the activational effects of androgens. Transsexuals treated with cross-sex hormones display sex reversals in their cognitive abilities, emotional tendencies, and libido (34, 35), and sex offenders are sometimes treated with antiandrogens to reduce their sex drive (36). The sociosexual changes observed in these groups most likely reflect structural and physiological plasticity in steroid-sensitive areas within the brain. The volumetric sex reversal reported here substantiates the possibility that hormones in adulthood can dramatically affect the structure of a brain region concerned with sexual behavior. Although the volumetric sexual dimorphism of the MePD is more modest than other animal models [a difference of 150% rather than 400–600% (31)], the extent of the MePD sexual dimorphism in rats in quite comparable to reported sexual dimorphisms in the human brain (1–6) and thereforesupports the possibility that sexual dimorphisms of the human brain are caused solely by circulating steroids in adulthood.”

We can’t generalize from a study of rat brains to human brains, but this study does underline the importance of using trans people who have not taken cross-sex hormones if you want to study gender identity and the brain.